Description: This is a competitive renewal application from Dr. Welgus to investigate various aspects of the control of collagenase and matrix- metalloproteinase (MMP) production by human keratinocytes in culture. The specific aims are to: 1) define matrix components which induce collagenase production by cultured keratinocytes, identify the cell surface recognition integrins that mediate the induction, and study the signal transduction pathways; 2) define the mechanism of matrix-induced collagenase expression, by identifying cis-acting promoter elements in the collagenase 5' flanking region of the gene, and identify trans acting factors that bind to these sequences and modulate gene expression; 3) determine the factors and gene regulatory mechanisms controlling the expression of stromelysin-1 and stromelysin-2, which are apparently expressed in vivo in wound repair by distinctly different populations of keratinocytes; and 4) study collagenase and stromelysin-1 and -2 expression in a skin-equivalent model of keratinocyte cultures after wounding.